Erythropoietin prevents PC12 cells from beta-amyloid-induced apoptosis via PI3K⁄Akt pathway

Translational Neurodegeneration

Chen Sheng-Di³  Hong Zhen¹  Pan Jing¹  Wang Zhi-Quan³  Yang Hong-Qi¹  Sun Zhi-Kun² 

[1] Department of Neurology & Institute of Neurology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, People's Republic of China;Department of Neurology & Institute of Neurology, Henan Provincial Hospital, Zhengzhou City, Henan province 450000, People's Republic of China;Lab of Neurodegenerative Diseases, Institute of Health Science, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) & Shanghai Jiaotong University School of Medicine, Shanghai 200025, People's Republic of China

关键词: Alzheimer's disease;    Erythropoietin;    Apoptosis;    Beta-amyloid peptide;   

Others  :  839018
DOI  :  10.1186/2047-9158-1-7

 received in 2011-12-31, accepted in 2012-02-29,  发布年份 2012

【 摘 要 】

Background

Several studies indicated that Erythropoietin (Epo) may provide remarkable neuroprotection in some neurological diseases. It also showed the significant decrease of Epo immunoreactivity in the cerebral cortex and hippocampus in aged rats, suggesting the role of Epo in the pathogenesis of age-related neurodegenerative diseases such as AD.

Methods

The protective effect of Epo was studied in differentiated PC12 cells treated with Abeta. The viability of the cells, the apoptosis of the cells and the level of Bax, Bcl-2, cleaved caspase-3 and cleaved PARP expression were detected by MTT, Hoechst 33258 staining and Western blotting respectively.

Results

20 μM Abeta _(25-35) could induce a decreased viability and a increased apoptosis in PC12 cell in a time-dependent manner. However, 20 μM Abeta _(35-25) had no effect on cell viability and apoptosis. Western blot analysis also showed that Abeta_(25-35) treatment could decrease the expression of Bcl-2 (P < 0.05) and increase the expression of Bax (P < 0.05), Cleaved casapase-3 (P < 0.05), and Cleaved PARP (P < 0.05). The pretreatment of Epo could effectively reverse all the above changes induced by Abeta_(25-35) (P < 0.05). Furthermore, the protective effect of Epo could be blocked by PI3K inhibitor LY294002 (P < 0.05).

Conclusions

Epo prevented cell injuries in PC12 cells exposed to the Abeta_(25-35) and this effect may depend on the PI3K⁄Akt pathway. Our study provided an important evidence for the potential application of Epo in the therapy of Alzheimer's disease.

【 授权许可】

   
2012 Zhi-Kun et al; licensee BioMed Central Ltd.

【 图 表 】

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